We plan to determine whether serologically-defined lymphocyte surface membrane markers unique to insulin-dependent diabetes (IDDM) exist, and their relationship to HLA. The known association of HLA-DRw3 and DRw4 with IDDM is consistent with linkage disequilibrium with an as yet undefined HLA-linked gene. Preliminary results with antisera of ill-defined DR specificity which have a high reaction rate with IDDM cells suggests that such an antigen system may exist. We will screen the sera from multiparous females exposed by pregnancy to the putative IDDM antigen, and will test linkage and inheritance in families having multiple cases of IDDM, including families with conjugal diabetes.